Quinoxaline lactone

Reaction of commercially available 3-chlorotetronic acid 762, obtained by pyrolysis of methyl 2,4-dichloroacetoacetate at 140 °C in vacuo [235], with o-phenylene-diamine affords, after cyclization-oxidation with AgOAc, the quinoxaline lactone 763 in 69% yield [234] (Scheme 5.83). 

Oxidation of L-ascorbic (702) or D-isoascorbic acid (703) with p-benzoquinone followed by MWI with two equivalents of o-phenylenediamine for 1 min gave 87-94% yields of quinoxaline 726. Acid hydrolysis of 726 was also achieved under MWI for 3 min to give the corresponding quinoxaline lactone 727 in 48-53% yields (Scheme 140) (05UP4). The yields were higher with a shorter reaction time than conventional methods (92AHC233, 00MI6). 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

The reaction of pyrazine and quinoxaline with methyl chloroformate and bis-silyl enol ethers gave fused tetrahydropyrazine lactones 88, in an extension of previous work. There was little consistency with the variation of R in the stereochemistry of the products <06T12084>. 

The lactone 223 was isolated from 2-benzoyl-3-hydroxymethylquin-oxaline 1-oxide 221 on treatment with alkali and subsequent acidification, probably by intramolecular Cannizzaro reaction of 2-benzoyl-3-quinoxaline carboxyaldehyde (222), which in turn is obtained from 221 by a series of tautomeric shifts and 1,4-elimination.221... 

DCC is also used to prereact carboxyl groups with 0-benzylhydroxylamine prior to /8-lactam ring closure. A water soluble carbodiimide in combination with HOBt is used in several steps of the total synthesis of nisin, a pentacyclic polypeptide. Carbodiimides are also used for amide bond formation in the synthesis of the antiviral antibiotic distamycin Similarly, carbodiimides are used in the synthesis of a model depsipeptide lactone related to quinoxaline antibiotics. In the last synthesis, DCC in the presence of pyridine is used in the depsipeptide bond formation. 

This reaction has wide application in the preparation of aldehydes, ketones, lactones, quinones, and quinoxalines. 

Another group of cytostatic, antiviral and antibacterial yet highly toxic peptides are the quinoxalines [64] with two quinoxaline-carboxylic acids attached to eight membered, disulfide bridged symmetric peptide-lactone rings. Further inhibitors of protein biosynthesis isolated from Streptomyces species here mentioned only by name are streptogramin B and the tuberactinomycins (e.g. Viomycin) isolated, elucidated and synthesized mainly by T. Shiba s group in Osaka. 

Ketenes are mostly used as common starting materials for structurally diverse mono-spiro- and fused six-membered heterocycles such as lactones, pyrans, pyronones, pyridines, quinolines, isoquinolines, oxazine, quinoxalines, thiazines, oxathines, etc. 

Polarographic studies of 2,3-diketo-L-gulonic acid (i.e. L-r/ireo-hex-2,3-diulosonic acid, the hydrolysis product of dehydroascorbic acid) and the 2,3- and 3,4-endiol forms of its 1,5-lactone have been reported. On condensation with a-phenylenediamine, these compounds form a single product, 2-(2-aminophenyl)-3-(L-f/ireo-triitol-l-yl)quinoxaline, that gives a well defined cathodic wave suitable for analytical purposes. "... 

As an a-keto lactone, phenylhydrazone 500 (2//-chromene derivative) reacts with 1,2-DAB 155a in a boiling EtOH/AcOH mixture, with ring cleavage giving rise to quinoxalin-2-(lH)-one 502 (Scheme 2.113) (Vinot et al. 1983). 

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